Tropomyosin position on F-actin revealed by EM reconstruction and computational chemistry
AuthorsLi, Xiachuan Edward
Tobacman, Larry S.
Mun, Ji Young
Craig, Roger W.
UMass Chan AffiliationsDepartment of Cell Biology
Document TypeJournal Article
Image Processing, Computer-Assisted
Reproducibility of Results
MetadataShow full item record
AbstractElectron microscopy and fiber diffraction studies of reconstituted F-actin-tropomyosin filaments reveal the azimuthal position of end-to-end linked tropomyosin molecules on the surface of actin. However, the longitudinal z-position of tropomyosin along F-actin is still uncertain. Without this information, atomic models of F-actin-tropomyosin filaments, free of constraints imposed by troponin or other actin-binding proteins, cannot be formulated, and thus optimal interfacial contacts between actin and tropomyosin remain unknown. Here, a computational search assessing electrostatic interactions for multiple azimuthal locations, z-positions, and pseudo-rotations of tropomyosin on F-actin was performed. The information gleaned was used to localize tropomyosin on F-actin, yielding an atomic model characterized by protein-protein contacts that primarily involve clusters of basic amino acids on actin subdomains 1 and 3 juxtaposed against acidic residues on the successive quasi-repeating units of tropomyosin. A virtually identical model generated by docking F-actin and tropomyosin atomic structures into electron microscopy reconstructions of F-actin-tropomyosin validated the above solution. Here, the z-position of tropomyosin alongside F-actin was defined by matching the seven broad and narrow motifs that typify tropomyosin's twisting superhelical coiled-coil to the wide and tapering tropomyosin densities seen in surface views of F-actin-tropomyosin reconstructions. The functional implications of the F-actin-tropomyosin models determined in this work are discussed. rights reserved.
SourceBiophys J. 2011 Feb 16;100(4):1005-13. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/26424
Related ResourcesLink to Article in PubMed